• Natural Product Sciences
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• 제10권5호
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• pp.228-236
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• 2004

The aim of the present study was to examine whether green tea extract (CUMC6335) affects the blood pressure and the isolated aortic contractility of the rabbit in comparison with one of the most powerful active catechins, epigallocatechin gallate (EGCG). The phenylephrine $(1-10\;{\mu}M)-induced$ contractile responses were greatly inhibited in the presence of CUMC6335 (0.3-1.2 mg/ml). Also, high potassium (56 mM)-induced contractile responses were depressed in high concentration (0.6-1.2 mg/ml), but not affected in low concentration CUMC6335 (0.3 mg/ml). However, epigallocatechin gallate $(EGCG,\;4-12\;{\mu}g/ml)$ did not affect the contractile responses evoked by phenylephrine and high $K^+$. The infusion of CUMC6335 with a rate of 20 mg/kg/30 min made a significant reduction in pressor responses induced by intravenous norepinephrine. However, EGCG (1 mg/kg/30 min) did not affect them. Collectively, these results obtained from the present study suggest that intravenous CUMC6335 causes depressor action in the anesthetized rat at least partly through the blockade of adrenergic ${\alpha}_1-receptors$. CUMC6335 also causes the relaxation in the isolated aortic strips of the rabbit partly via the blockade of adrenergic ${\alpha}_1-receptors$, in addition to the unknown direct mechanism. It seems that there is no species difference in the vascular effect between the rat and the rabbit.

• 약학회지
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• 제41권2호
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• pp.247-254
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• 1997

The proteinase-activated receptor (PAR-2) belongs to the family of seven transmembrane region receptors, like the thrombin receptor, it is activated by specific proteolytic clea vage of its extracellular amino terminus and a synthetic peptide (SLIGRL). The earthworm protein fraction (EPF) extracted from Lumbricus rubellus elicted dose- and endothelium-dependent relaxations in phenylephrine-contracted rat thoracic aorta, whereas heat inactivated EPF (0.5 ${\mu}g$ /ml) had no effect. In the presence of the nitric oxide synthase inhibitor NG-methyl-L-arginine (1.8 micro M), EPF (0.5 ${\mu}g$ /ml)-induced relaxations were partially inhibited. Furthermore, EPF (0.5 ${\mu}g$ /ml) dramatically caused relaxation of thrombin-desenstized rat thoracic aorta. These results indicate that EPF activates PAR-2 in vascular endothelial cell. Intravenous injection of EPF (20 mg/kg, bolus) into anesthetized rats produced a marked depressor response. EPF (0 ~ 80 ${\mu}g$ /ml, gradient) was very effective on increasing of perfusion volume in rabbit ear vessel preparations. These results imply the usefulness of EPF as a vascular smooth muscle relaxant and indicate that the activation of PAR-2 may be a mechanism of EPF on hemokinetic improvement.

• Journal of Pharmaceutical Investigation
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• 제8권1호
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• pp.6-16
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• 1978

We obtained 4 kinds of extract fraction from Acanthopanacis Radicis Cortex and studied on the influence to the blood pressure of rabbit. These 4 fractions were obtained as follows; Fraction I was insoluble fraction by 99% ethanol from 80% methanol extract of Acanthopanacis Radicis Cortex, fraction II, precipitated fraction by ether from 99% ethanol soluble fraction of 80% methanol extract of Acanthopanaacis Radicis Cortex, fraction III, no precipitated fraction by ether from 99% ethanol soluble fraction of above 80% methanol extract and fraction IV, water extract of Acanthopanacis Radicis Cortex. All of fractions, when administered into ear-vein of rabbit, produced fall of blood pressure. Among these 4 fractions, although fraction III was not only the most potent but had the greatest efficacy, we observed the mechanism of hypotensive action of Acanthopanacis Radicis Cortex, making use of fraction II which was thought as a comparatively pure fraction. Hypotensive action of fraction II (APF II) was not affected by vagotominization but markedly inhibited by atropine. Pretreatment of bethanidine showed a tendency to weaken the depressor action of APF II, although it was not a significant result, but diphenhydramine did not influence APF II action. Phentolamine, guanethidine and chlorisondamine inhibited significantly the hypotensive action of APF II. APF II elicited the potentiation of norepinphrine pressor action dependent on the time-factor whereas it did not influence angiotesin pressor action. It is seemed that APF II exhibited hypotensive action, causing peripheral muscarinic-effect and centrally induced sympatholytic action.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.345-351
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• 1998

The role of nitric oxide (NO) in the hemorrhagic hypotension was examined using a NO synthase inhibitor, $N^{\omega}-nitro-L-arginine$ methyl ester (L-NAME), in conscious rats. The rats were bled at a constant rate (2 ml/kg/min) through a femoral arterial catheter until the mean arterial pressure (MAP) was reduced by 50 mmHg. We studied the responses to hemorrhage under normal condition (Control) and after the pretreatment with 3 doses of L-NAME (1.6, 8, 40 mg/kg i.v. of NOX1.6, NOX8, and NOX40, respectively). Intravenous bolus injection of L-NAME produced a sustained increase in MAP and decrease in heart rate (HR). During hemorrhage, the MAP fell faster in the NOX8 and NOX40-treated groups than in Control group, but the control group showed same response to NOX1.6. HR greatly increased in NOX groups. The recovery from hemorrhagic hypotension was slowed in the control group, which was not treated with L-NAME. In comparison with the control group, NOX8 and NOX1.6-treated groups registered a significant recovery in MAP during the 15 min recovery period, but NOX40 brought about only a slight increase in MAP. NO precursor, L-arginine (150 mg/kg i.v.), produced significant bradycardic responses before and after hemorrhage and significant depressor response only after hemorrhagic hypotension regardless of pretreatment with L-NAME. These data suggest that the role of NO in blood pressure regulation is greater after hemorrhagic hypotension than basal condition, but the effect of NO can be detrimental to the recovery from hemorrhagic hypotension. In addition, the bradycardic response of L-arginine provides indirect evidence that NO may inhibit sympathetic activity, especially after hemorrhagic hypotension.

• Journal of Pharmaceutical Investigation
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• 제8권3호
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• pp.16-23
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• 1978

This study was carried out for the purpose of observing the effect of Korean Acanthopanax Radicis Cortex on renal hypertension and to clarify the mechanism of this effect, making use of its ethanol extract. Adult male or female rats, weighing 180-250g, were divided into 3 groups; the first for normotensive control, the second for hypertensive control and the third for hypertensive Acantopanax-treatment. Rats in the normotensive and hypertensive control group were administered 0.9% saline subcutaneously only, whereas those in the Acanthopanax-treated hypertensive group were administered 50mg/kg Acanthopanax ethanol extract subcutanously once a day. Changes of original blood pressure, and responses of blood pressure to various 4gents(norepinephrine, angiotensin, acetylcholine, serotonin and histamine) were recorded for each group on the initial, 18th, 32nd and 46th days of the experiment. The results obtained in this experiment are as follows: 1) The initial blood pressure was $102.6{\pm}7.6mmHg$ on the average. The blood pressures of the normotensive control group were not observed to alter significantly at any period in the course of the experiment. 2) The mean blood pressures in the hypertensive control group were recorded at $120.3{\pm}10.4mmHg$ on the 18th day, at $134.5{\pm}9.2$ on the 32nd day and at $138.8{\pm}8.3$ on the 46th day, thus revealing significant elevation in comparison with the corresponding normotensive control group blood pressures. On the other hand, the mean blood pressures in Acanthopanax-treated hypertensive group on the 18th, 32nd and 46th days were $118.3{\pm}9.7,\;129.9{\pm}8.3\;and\;120.2{\pm}8.3mmHg$ respectively. The blood pressures of the hypertensive-Acanthopanax group recorded. on the 46th day revealed a significant difference as compared with those of the corresponding hypertensive control group. 3) On the 46th day of this experiment, the responses of blood pressure to acetylcholine in the hypertensive-Acanthopanax group were suppressed significantly as compared with those of the hypertensive control group, and in the latter group, angiotensin was decreased markedly as compared with the corresponding normotensive control group. In contrast, pressor action of norepinephrine and depressor action of serotonin and histamine did not differ significantly among the three groups. These results suggest that Acanthopanax ethanol extract suppresses the induction of renal hypertension by means of a cholinergic action such as that caused by acetylcholine.

• 대한약리학회지
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• 제29권2호
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• pp.213-223
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• 1993

급성 신성 고혈압쥐 (2-kidney, 1-ligation type)의 전신성 동맥계와 폐 동맥계에 대한 내피 의존적 혈관반응성을 규명하기 위하여, 적출 혈관 및 마취상태의 흰쥐에 대한 acetylcholine (ACh)의 혈관이완작용 및 혈압강하 작용을 측정하였다. 혈장 renin 활성(PRA)은 신동맥 결찰전 $7.31{\pm}0.63\;ng/ml/hr$ A I에 비해 결찰 $6{\sim}8$일후에는 $19{\sim}22\;ng/ml/hr$ A I으로 유의성있게 증가하였으며, 이는 수축기혈압의 상승과 $(154{\pm}1.83{\rightarrow}190{\sim}215\;mmHg)$ 일정한 상관성을 유지하였다. 신성 고혈압쥐 및 정상 혈압쥐의 흉곽 대동맥은 내피세포 존재시 ACh에 의해 용량의존적으로 이완되었으며, 이때 신성고혈압쥐에서의 반응은 정상 혈압쥐에 비해 유의성있게 감소하였다(각각 34% 및 86%, p<0.01). 또한 ACh은 신성 고혈압쥐 및 정상 혈압쥐의 폐동맥에 대해서도 내피세포 존재시에 이완반응을 초래하였다. 그러나, 흉곽 대동맥에서와는 달리 두 군간에 유의성있는 차이가 없었다. 이들 반응은 내피세포 제거후 또는 EDRF 억제제 (L-NAME, MB, $10^{-5}$ M) 투여후 유의성있게 억제되었다. $ACh(0.1{\sim}10\;{\mu}g/kg,\;i.v.)$은 신성 고혈압쥐 및 정상 혈압쥐에서 전신성 동맥압의 강하를 초래하였는데, 신성 고혈압쥐에서 다소 감소하였으나 유의성있는 차이는 없었으며 ($SAPm;\;10\;{\mu}g/kg$에서 각각 39%, 46 %), 이들 작용은 L-NAME(30 mg/kg, i.v.) 전처치후 유의성있게 억제되었다. ACh에 의한 폐동맥압 강하는 신성 고혈압쥐 및 정상 혈압쥐 사이에 서로 비슷하게 나타났다. 그러나, 신성 고혈압 쥐 및 정상 혈압쥐에서 ACh에 의한 폐동맥압의 강하율은 전신성 동맥압의 강하율보다 유의성있게(p<0.01) 작았으며, 또한 L-NAME $(0.1{\sim}100\;mg/kg,\;i.v.)$에 의한 폐동맥압의 상승은 전신성 동맥압의 상승보다 유의성있게(p<0.01) 작았다. 이상의 실험 결과들은 급성 신성 고혈압쥐의 전신성 동맥계에서는 내피세포 손상이 초래되지만, 폐동맥계에서는 초래되지 않는다는것을 제시해준다. 또 신성고혈압쥐 및 정상 혈압쥐에서 EDRF 의 basal release 및 ACh 유발성 EDRF function은 전신성 동맥계에 비해 폐동맥계에서 적다는 것을 제시해준다.

• 대한약리학회지
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• 제28권1호
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• pp.27-40
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• 1992

Taurine은 유황 함유 아미노산으로서 뇌내에서 억제작용을 갖는 신경전달물질 역할을 하는것으로 알려져 있다. Taurine을 가토의 측뇌실내에 투여하여 혈압 및 심박에 미치는 영향을 검토하고 그 작용 기전을 규명코자 본 연구를 시행하여 얻은 연구결과는 다음과 같다. Taurine $(0.15{\sim}1.5\;mg)$은 urethane 마취 가토의 측뇌실내로 주사하였을때 혈압강하작용 및 심박감소작용이 현저하고 지속적인 용량반응 곡선을 나타내었다. 이와 동시에 상당한 호흡억제 작용도 관찰되었다. 그러나 동일량의 taurine을 정맥내에 투여시 혈압 및 심박에 아무런 영향을 미치지 못하였다. Taurine의 혈압 하강작용은 chlorisondamine, clonidine, strychnine, bicuculline등으로 전처치시 유의하게 억제되었으나 atropine, 양측 미주신경절단, propranolol 및 metoclopramide등의 전처치로 영향을 받지 않았다. 더우기 taurine은 norepinephrine의 승압 반응에도 영향을 미치지 못하였다. Taurine의 심박감소 작용은 chlorisondamine, propranolol, clonidine, strychnine 및 bicuculline등으로 전처리시 현저히 차단되었으나 atropine, 양측 미주신경절단, metoclopramide 등의 전처리로 영향을 받지 않았다. 이상의 연구한 결과로 보아, taurine은 가토의 측뇌실내 투여시 지속적이며 현저한 혈압하강 및 심박감소를 일으키며 이러한 작용은 뇌내의 catecholamine 뉴론과 관련있는 taurine (glycine) 및 gamma-aminobutyric acid (GABA) 수용체를 통해서 나타나는 것으로 사료된다.

• 대한약리학회지
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• 제13권2호
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• pp.19-34
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• 1977

1) 마취가토(痲醉家兎) 및 묘(猫)에서 경뇌막외강(硬腦膜外腔)을 통(通)한 가압방법(加壓方法)으로 두개내압상승(頭蓋內驅上昇)과 혈압(血壓) 및 심박(心搏)과의 관계(關係)를 조사(調査)하였다. 2) 양동물(兩動物)에서 두개내압(頭盞內壓)을 상승(上昇)시켜 두개내압(頭蓋內壓)과 혈압(血壓)의 차(差)가 아주 적어지면 현저(顯著)한 혈압상승(血壓上昇)이 나타났다. 3) 양동물(兩動物)에서 두개내압(頭盞內壓)이 혈압(血壓)보다 높아지면 현저(顯著)한 혈압하강(血壓下降)과 현저(顯著)한 일시적(一時的)인 심박감소(心搏減少)가 나타났다. 4) Reserpine 처리동물(處理動物)에서는 두개내압상승(頭蓋內驅上昇)은 혈압하강(血壓下降), 심박감소(心搏減少)를 일으켰다. 5) 6-Hydroxydopamine 처리(뇌내)동물(處理(腦內)動物)에서는 두개내압상승(頭蓋內驅上昇)에 의한 혈압상승(血壓上昇)은 비처리동물(非處理動物)에 비(比)하여 약(弱)하였다. 6) Reserpine 처리동물(處理動物)의 측뇌실내(側腦室內)에 norepinephrine을 투여(投與)한 후(後)에는 두개내압상승(頭蓋內驅上昇)은 현저(顯著)한 혈압상승(血壓上昇)을 일으켰다. 7) 두개내압상승(頭蓋內驅上昇)에 의한 혈압상승(血壓上昇)은 두개내압상승(頭蓋內驅上昇)으로써 뇌내(腦內) noradrenergic neuron이 자극(刺戟)되여 norepinephrine 유리(遊離)가 증가(增加)한 결과(結果) 일어나는 것으로 추리(推理)하였다.